Skin photoaging is induced and sustained by UV-induced oxidative damage,and stimulating regeneration of the UV-induced aging has remained a great challenge due to high-level oxidative stress factor(ROS)-induced chroni...Skin photoaging is induced and sustained by UV-induced oxidative damage,and stimulating regeneration of the UV-induced aging has remained a great challenge due to high-level oxidative stress factor(ROS)-induced chronic oxidative damage and inactivation of bio-macromolecule-based regeneration in oxidative photoaging micro-environment.In this study,we designed a“seed and soil”strategy to pursue a safer and more efficient way to prevent and treat photoaging by simultaneously changing UV-induced ROS-rich micro-environment into a proregenerative one(the“soil”)and providing growth factor-rich platelet lysates(PL,the“seed”)using PL-impregnated,collagen-reinforce hydrogel(PL/Col).SD rats were used to establish photoaging model by 8 weeks of UV irradiation.The effectiveness of different treatments was evaluated by making pathological sections and detecting photoaging-related indicators.Rats treated with PL/Col demonstrated a significant acceleration in skin healing and enhancement in the quality of trauma repairing.After treated with PL/Col,the rats showed smooth yellowish appearance,integral structure of skin collagen fiber and epidermis,a decrease in inflammation and a reshaped active micro-environment with reduced levels of SOD enzyme activity,GSH enzyme activity and MDA toxic products.Treatment of PL/Col in skin photoaging has shown potential anti-oxidation and anti-aging effects and is worthy of further study in related field.展开更多
This research aims to develop a wound dressing composed of collagen (Col) and hyaluronic acid (HA) containing epidermal growth factor (EGF). First important issue is to contain EGF in the wound dressing in a stable st...This research aims to develop a wound dressing composed of collagen (Col) and hyaluronic acid (HA) containing epidermal growth factor (EGF). First important issue is to contain EGF in the wound dressing in a stable state. The sheet-shaped sponge was manufactured by freeze-vacuum drying an aqueous solution of Col. Both sides of sponge were treated with ultraviolet (UV) irradiation to introduce intermolecular cross links between collagen molecules. This sponge was named Sponge-Col. Another sheet-shaped sponge was manufactured by freeze-vacuum drying an aqueous solution of HA containing EGF. This sponge was named Sponge-HA/EGF. The wound dressing was manufactured by laminating Sponge-Col on the top, Sponge-HA/EGF in the middle, and Sponge-Col on the bottom to create a sandwich structure. This method can prevent the reducing of EGF activity due to UV irradiation for intermolecular cross-linking. Second important issue is to enable gradual release of EGF from the wound dressing. The elution behavior of this wound dressing was investigated by measuring the weight change after immersion in water for a predetermined time. This wound dressing showed initially fast elution and subsequent very slow elution properties. The upper layer and lower layer Sponge-Col enabled gradual release of the middle layer Sponge-HA/EGF. This result suggests that EGF contained in the wound dressing is gradually released together with HA from the wound dressing. Third important issue is to provide moist wound-healing environment. The upper layer and lower layer Sponge-Col can provide the wound dressing with high water absorption and long-term water retention properties.展开更多
The role of vascular endothelial growth factor A in platelet adhesion in cerebral microvessels in the early stage of subarachnoid hemorrhage remains unclear.In this study,the endovascular puncture method was used to p...The role of vascular endothelial growth factor A in platelet adhesion in cerebral microvessels in the early stage of subarachnoid hemorrhage remains unclear.In this study,the endovascular puncture method was used to produce a rat model of subarachnoid hemorrhage.Then,30 minutes later,vascular endothelial growth factor A antagonist anti-vascular endothelial growth factor receptor 2 antibody,10μg,was injected into the right ventricle.Immunohistochemistry and western blot assay were used to assess expression of vascular endothelial growth factor A,occludin and claudin-5.Immunohistochemical double labeling was conducted to examine co-expression of GP Ⅰa-Ⅱ integrin and type Ⅳ collagen.TUNEL was used to detect apoptosis in the hippocampus.Neurological score was used to assess behavioral performance.After subarachnoid hemorrhage,the expression of vascular endothelial growth factor A increased in the hippocampus,while occludin and claudin-5 expression levels decreased.Co-expression of GP Ⅰa-Ⅱ integrin and type Ⅳ collagen and the number of apoptotic cells increased,whereas behavioral performance was markedly impaired.After treatment with anti-vascular endothelial growth factor receptor 2 antibody,occludin and claudin-5 expression recovered,while co-expression of GP Ⅰa-Ⅱ integrin and type Ⅳ collagen and the number of apoptotic cells decreased.Furthermore,behavioral performance improved notably.Our findings suggest that increased vascular endothelial growth factor A levels promote platelet adhesion and contribute to early brain injury after subarachnoid hemorrhage.This study was approved by the Biomedical Ethics Committee,Medical College of Xi’an Jiaotong University,China in December 2015.展开更多
Objective： To investigate the effects of connective tissue growth factor（CTGF） and collagen type I（COL-I） on the pathogenesis of scleroderma and explore the relationship between the level of COL-I and CTGF. Meth...Objective： To investigate the effects of connective tissue growth factor（CTGF） and collagen type I（COL-I） on the pathogenesis of scleroderma and explore the relationship between the level of COL-I and CTGF. Methods： 12 mice model of scleroderma was established by the injection of Bleomycin. The level of CTGF and COL-I were detected by immunohistochemical method. The relationship was analyzed between CTGF and COL-I level. As control group, 12 healthy mice were selected. Results： The levels of CTGF and COL-I in sclerotic models were higher than in normal controls （P 〈 0.05）. It was found that there was a correlation between the level of CTGF and COL-I. Conclusion： CTGF and COL-I played an important role in the hardening process of the skin lesions of the mice model, which may be involved in the pathogenesis of scleroderma.展开更多
Objective: To explore the effects of connective tissue growth factor (CTGF) on the pathogenesis of human keloid. Methods: CTGF antisense oligonucleotides (ASODN) conjugated with isothiocyananate fluorescence was encap...Objective: To explore the effects of connective tissue growth factor (CTGF) on the pathogenesis of human keloid. Methods: CTGF antisense oligonucleotides (ASODN) conjugated with isothiocyananate fluorescence was encapsulated by liposome, and then added into the human keloid fibroblasts (HKFs) culture media. The intracellular distribution of CTGF ASODN was observed by fluorescence microscopy in the fixed HKFs. The proliferation of HKFs was measured by MTT test. The collagen synthesis of HKFs was measured by 3H-proline incorporation method. Results: Compared with control group, the CTGF ASODN can inhibit the proliferation and collagen synthesis of the HKFs (P<0.01). Conclusion: CTGF ASODN has anti-fibrotic effects on keloid in vitro, and CTGF play an important role in promoting the fibrosis of keloid.展开更多
Insulin-like growth factor 1 （IGF-I） is a potential nutrient for nerve repair. However, it is impractical as a therapy because of its limited half- life, rapid clearance, and limited target specificity. To achieve t...Insulin-like growth factor 1 （IGF-I） is a potential nutrient for nerve repair. However, it is impractical as a therapy because of its limited half- life, rapid clearance, and limited target specificity. To achieve targeted and long-lasting treatment, we investigated the addition of a binding structure by fusing a collagen-binding domain to IGF- 1. After confirming its affinity for collagen, the biological activity of this construct was examined by measuring cell proliferation after transfection into PC12 and Schwann cells using a 3-（4,5-dimethyl-2-thiazolyl）-2,5-di- phenyl-2-H-tetrazolium bromide assay. Immunofluorescence staining was conducted to detect neurofilament and microtubule-associated protein 2 expression, while real time-polymerase chain reaction was utilized to determine IGF-1 receptor and nerve growth/actor mRNA expression. Our results demonstrate a significant increase in collagen-binding activity of the recombinant protein compared with IGF-1. Moreover, the recombinant protein promoted proliferation of PC12 and Schwann cells, and increased the expression of neurofilament and microtubule-associated protein 2. Importantly, the recombinant protein also stimulated sustained expression of IGF-1 receptor and nerve growth factor mRNA for days. These results show that the recombinant protein achieved the goal of targeting and long-lasting treatment, and thus could become a clinically used factor for promoting nerve regeneration with a prolonged therapeutic effect.展开更多
All tissues in the body are subjected externally to gravity and internally by collagenfibril and cellular retractive forces that create stress and energy equilibrium required for homeostasis.Mechanotransduction involve...All tissues in the body are subjected externally to gravity and internally by collagenfibril and cellular retractive forces that create stress and energy equilibrium required for homeostasis.Mechanotransduction involves mechanical work(force through a distance)and energy storage as kinetic and potential energy.This leads to changes in cell mitosis or apoptosis and the synthesis or loss of tissue components.It involves the application of energy directly to cells through integrin-mediated processes,cell-cell connections,stretching of the cell cytoplasm,and activation of the cell nucleus via yes-associated protein(YAP)and transcriptional coactivator with PDZ-motif(TAZ).These processes involve numerous complexes,intermediate molecules,and multiple pathways.Several pathways have been identified from research studies on vertebrate cell culture and from studies in invertebrates.These pathways involve mechanosensors and other molecules that activate the pathways.This review discusses the mitogen-activated protein kinase(MAPK)family,Hippo,Hedgehog,and Wingless-related integration site(WNT)/βcatenin signaling pathways.The mediators covered includeβcatenin,ion channels,growth factors,hormone receptors,members of the Ras superfamily,and components of the linker of nucleoskeleton and cytoskeleton(LINC)complex.However,the interrelationship among the different pathways remains to be clarified.Integrin-mediated mechanotransduction involves direct tensile loading and energy applied to the cell membrane via collagenfibril stretching.This energy is transferred between cells by stretching the cell-cell connections involving cadherins and the WNT/βcatenin pathway.These alterations induce changes in intracellular events in the cytoskeleton and nuclear skeleton caused by the release of YAP and TAZ.These coactivators then penetrate through the nuclear pores and influence nuclear cell function.Alteration in the balance of forces and energy applied to cells and tissues is hypothesized to shift the cell-extracellular matrix mechanical equilibrium by modifying mechanotransduction.The shift in equilibrium can lead to either tissue synthesis,genetic modifications,or promotefibrotic diseases,including epithelial cell-derived cancers,depending on the local metabolic conditions.展开更多
背景:腰椎间盘退行性疾病是导致腰痛和下肢神经症状的常见疾病。胶原代谢的平衡在维持椎间盘的稳定中发挥着重要的作用。目的:对椎间盘退变中胶原蛋白代谢失衡的研究进展作一综述。方法:由第一作者在中国知网、PubMed、Web of Science...背景:腰椎间盘退行性疾病是导致腰痛和下肢神经症状的常见疾病。胶原代谢的平衡在维持椎间盘的稳定中发挥着重要的作用。目的:对椎间盘退变中胶原蛋白代谢失衡的研究进展作一综述。方法:由第一作者在中国知网、PubMed、Web of Science数据库中检索2024年5月之前发表的相关文章,中文检索词为“椎间盘退变疾病”“胶原代谢”“胶原酶家族”“胶原合成相关因子”“细胞因子”,英文检索词为“degenerative disc disease”“Collagen metabolism”“Collagenase family”“Collagen synthesis related factors”“Collagen breakdown related factors”。最终纳入76篇文献进行综述。结果与结论:在椎间盘退变的过程中,胶原蛋白代谢的平衡在维持正常椎间盘的稳定中起到至关重要的作用。当椎间盘发生退变时,椎间盘内分泌大量促炎因子、胶原酶,并发生氧化应激反应等,使椎间盘内胶原蛋白分解增加,同时抑制生长因子、胶原蛋白合成酶、胶原蛋合成相关因子的生成,使椎间盘内胶原蛋白合成减少。上述两种情况共同作用使椎间盘内胶原蛋白的代谢平衡被打破,进一步加剧了椎间盘退变的进程。展开更多
基金funding from the Discipline construction project of Guangdong Medical University(4SG21277P,2021ZDZX2039,2DK21003,4SG23060G)Our work described in the present manuscript was also supported by research grants from Guangdong Provincial Natural Science Foundation(2021A1515012437,2021KTSCX040),Guangdong,China。
文摘Skin photoaging is induced and sustained by UV-induced oxidative damage,and stimulating regeneration of the UV-induced aging has remained a great challenge due to high-level oxidative stress factor(ROS)-induced chronic oxidative damage and inactivation of bio-macromolecule-based regeneration in oxidative photoaging micro-environment.In this study,we designed a“seed and soil”strategy to pursue a safer and more efficient way to prevent and treat photoaging by simultaneously changing UV-induced ROS-rich micro-environment into a proregenerative one(the“soil”)and providing growth factor-rich platelet lysates(PL,the“seed”)using PL-impregnated,collagen-reinforce hydrogel(PL/Col).SD rats were used to establish photoaging model by 8 weeks of UV irradiation.The effectiveness of different treatments was evaluated by making pathological sections and detecting photoaging-related indicators.Rats treated with PL/Col demonstrated a significant acceleration in skin healing and enhancement in the quality of trauma repairing.After treated with PL/Col,the rats showed smooth yellowish appearance,integral structure of skin collagen fiber and epidermis,a decrease in inflammation and a reshaped active micro-environment with reduced levels of SOD enzyme activity,GSH enzyme activity and MDA toxic products.Treatment of PL/Col in skin photoaging has shown potential anti-oxidation and anti-aging effects and is worthy of further study in related field.
文摘This research aims to develop a wound dressing composed of collagen (Col) and hyaluronic acid (HA) containing epidermal growth factor (EGF). First important issue is to contain EGF in the wound dressing in a stable state. The sheet-shaped sponge was manufactured by freeze-vacuum drying an aqueous solution of Col. Both sides of sponge were treated with ultraviolet (UV) irradiation to introduce intermolecular cross links between collagen molecules. This sponge was named Sponge-Col. Another sheet-shaped sponge was manufactured by freeze-vacuum drying an aqueous solution of HA containing EGF. This sponge was named Sponge-HA/EGF. The wound dressing was manufactured by laminating Sponge-Col on the top, Sponge-HA/EGF in the middle, and Sponge-Col on the bottom to create a sandwich structure. This method can prevent the reducing of EGF activity due to UV irradiation for intermolecular cross-linking. Second important issue is to enable gradual release of EGF from the wound dressing. The elution behavior of this wound dressing was investigated by measuring the weight change after immersion in water for a predetermined time. This wound dressing showed initially fast elution and subsequent very slow elution properties. The upper layer and lower layer Sponge-Col enabled gradual release of the middle layer Sponge-HA/EGF. This result suggests that EGF contained in the wound dressing is gradually released together with HA from the wound dressing. Third important issue is to provide moist wound-healing environment. The upper layer and lower layer Sponge-Col can provide the wound dressing with high water absorption and long-term water retention properties.
基金financially supported by the National Natural Science Foundation of China,No.81471179(to JNS)
文摘The role of vascular endothelial growth factor A in platelet adhesion in cerebral microvessels in the early stage of subarachnoid hemorrhage remains unclear.In this study,the endovascular puncture method was used to produce a rat model of subarachnoid hemorrhage.Then,30 minutes later,vascular endothelial growth factor A antagonist anti-vascular endothelial growth factor receptor 2 antibody,10μg,was injected into the right ventricle.Immunohistochemistry and western blot assay were used to assess expression of vascular endothelial growth factor A,occludin and claudin-5.Immunohistochemical double labeling was conducted to examine co-expression of GP Ⅰa-Ⅱ integrin and type Ⅳ collagen.TUNEL was used to detect apoptosis in the hippocampus.Neurological score was used to assess behavioral performance.After subarachnoid hemorrhage,the expression of vascular endothelial growth factor A increased in the hippocampus,while occludin and claudin-5 expression levels decreased.Co-expression of GP Ⅰa-Ⅱ integrin and type Ⅳ collagen and the number of apoptotic cells increased,whereas behavioral performance was markedly impaired.After treatment with anti-vascular endothelial growth factor receptor 2 antibody,occludin and claudin-5 expression recovered,while co-expression of GP Ⅰa-Ⅱ integrin and type Ⅳ collagen and the number of apoptotic cells decreased.Furthermore,behavioral performance improved notably.Our findings suggest that increased vascular endothelial growth factor A levels promote platelet adhesion and contribute to early brain injury after subarachnoid hemorrhage.This study was approved by the Biomedical Ethics Committee,Medical College of Xi’an Jiaotong University,China in December 2015.
文摘Objective： To investigate the effects of connective tissue growth factor（CTGF） and collagen type I（COL-I） on the pathogenesis of scleroderma and explore the relationship between the level of COL-I and CTGF. Methods： 12 mice model of scleroderma was established by the injection of Bleomycin. The level of CTGF and COL-I were detected by immunohistochemical method. The relationship was analyzed between CTGF and COL-I level. As control group, 12 healthy mice were selected. Results： The levels of CTGF and COL-I in sclerotic models were higher than in normal controls （P 〈 0.05）. It was found that there was a correlation between the level of CTGF and COL-I. Conclusion： CTGF and COL-I played an important role in the hardening process of the skin lesions of the mice model, which may be involved in the pathogenesis of scleroderma.
文摘Objective: To explore the effects of connective tissue growth factor (CTGF) on the pathogenesis of human keloid. Methods: CTGF antisense oligonucleotides (ASODN) conjugated with isothiocyananate fluorescence was encapsulated by liposome, and then added into the human keloid fibroblasts (HKFs) culture media. The intracellular distribution of CTGF ASODN was observed by fluorescence microscopy in the fixed HKFs. The proliferation of HKFs was measured by MTT test. The collagen synthesis of HKFs was measured by 3H-proline incorporation method. Results: Compared with control group, the CTGF ASODN can inhibit the proliferation and collagen synthesis of the HKFs (P<0.01). Conclusion: CTGF ASODN has anti-fibrotic effects on keloid in vitro, and CTGF play an important role in promoting the fibrosis of keloid.
基金supported by the National Natural Science Foundation of China,No.81350013a grant from the Jilin Provincial Science and Technology Plan of China,No.20160101027JC&SC201502001the Graduate Innovation Fund of Jilin University in China,No.2017031&2017176
文摘Insulin-like growth factor 1 （IGF-I） is a potential nutrient for nerve repair. However, it is impractical as a therapy because of its limited half- life, rapid clearance, and limited target specificity. To achieve targeted and long-lasting treatment, we investigated the addition of a binding structure by fusing a collagen-binding domain to IGF- 1. After confirming its affinity for collagen, the biological activity of this construct was examined by measuring cell proliferation after transfection into PC12 and Schwann cells using a 3-（4,5-dimethyl-2-thiazolyl）-2,5-di- phenyl-2-H-tetrazolium bromide assay. Immunofluorescence staining was conducted to detect neurofilament and microtubule-associated protein 2 expression, while real time-polymerase chain reaction was utilized to determine IGF-1 receptor and nerve growth/actor mRNA expression. Our results demonstrate a significant increase in collagen-binding activity of the recombinant protein compared with IGF-1. Moreover, the recombinant protein promoted proliferation of PC12 and Schwann cells, and increased the expression of neurofilament and microtubule-associated protein 2. Importantly, the recombinant protein also stimulated sustained expression of IGF-1 receptor and nerve growth factor mRNA for days. These results show that the recombinant protein achieved the goal of targeting and long-lasting treatment, and thus could become a clinically used factor for promoting nerve regeneration with a prolonged therapeutic effect.
文摘All tissues in the body are subjected externally to gravity and internally by collagenfibril and cellular retractive forces that create stress and energy equilibrium required for homeostasis.Mechanotransduction involves mechanical work(force through a distance)and energy storage as kinetic and potential energy.This leads to changes in cell mitosis or apoptosis and the synthesis or loss of tissue components.It involves the application of energy directly to cells through integrin-mediated processes,cell-cell connections,stretching of the cell cytoplasm,and activation of the cell nucleus via yes-associated protein(YAP)and transcriptional coactivator with PDZ-motif(TAZ).These processes involve numerous complexes,intermediate molecules,and multiple pathways.Several pathways have been identified from research studies on vertebrate cell culture and from studies in invertebrates.These pathways involve mechanosensors and other molecules that activate the pathways.This review discusses the mitogen-activated protein kinase(MAPK)family,Hippo,Hedgehog,and Wingless-related integration site(WNT)/βcatenin signaling pathways.The mediators covered includeβcatenin,ion channels,growth factors,hormone receptors,members of the Ras superfamily,and components of the linker of nucleoskeleton and cytoskeleton(LINC)complex.However,the interrelationship among the different pathways remains to be clarified.Integrin-mediated mechanotransduction involves direct tensile loading and energy applied to the cell membrane via collagenfibril stretching.This energy is transferred between cells by stretching the cell-cell connections involving cadherins and the WNT/βcatenin pathway.These alterations induce changes in intracellular events in the cytoskeleton and nuclear skeleton caused by the release of YAP and TAZ.These coactivators then penetrate through the nuclear pores and influence nuclear cell function.Alteration in the balance of forces and energy applied to cells and tissues is hypothesized to shift the cell-extracellular matrix mechanical equilibrium by modifying mechanotransduction.The shift in equilibrium can lead to either tissue synthesis,genetic modifications,or promotefibrotic diseases,including epithelial cell-derived cancers,depending on the local metabolic conditions.
文摘背景:腰椎间盘退行性疾病是导致腰痛和下肢神经症状的常见疾病。胶原代谢的平衡在维持椎间盘的稳定中发挥着重要的作用。目的:对椎间盘退变中胶原蛋白代谢失衡的研究进展作一综述。方法:由第一作者在中国知网、PubMed、Web of Science数据库中检索2024年5月之前发表的相关文章,中文检索词为“椎间盘退变疾病”“胶原代谢”“胶原酶家族”“胶原合成相关因子”“细胞因子”,英文检索词为“degenerative disc disease”“Collagen metabolism”“Collagenase family”“Collagen synthesis related factors”“Collagen breakdown related factors”。最终纳入76篇文献进行综述。结果与结论:在椎间盘退变的过程中,胶原蛋白代谢的平衡在维持正常椎间盘的稳定中起到至关重要的作用。当椎间盘发生退变时,椎间盘内分泌大量促炎因子、胶原酶,并发生氧化应激反应等,使椎间盘内胶原蛋白分解增加,同时抑制生长因子、胶原蛋白合成酶、胶原蛋合成相关因子的生成,使椎间盘内胶原蛋白合成减少。上述两种情况共同作用使椎间盘内胶原蛋白的代谢平衡被打破,进一步加剧了椎间盘退变的进程。
